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Biomedical subjects

T B Cooper

Publications and source records attributed to T B Cooper.

At least 19 recordsLinked to original sources
PubMed1992

Serotonergic function in obsessive-compulsive disorder. Behavioral and neuroendocrine responses to oral m-chlorophenylpiperazine and fenfluramine in patients and healthy volunteers.

To evaluate serotonergic (5-hydroxytryptamine) function in obsessive-compulsive disorder, behavioral and neuroendocrine responses to m-chlorophenylpiperazine (m-CPP; 0.5 mg/kg orally) and fenfluramine hydrochloride (60 mg orally) were examined in 20 patients and 10 healthy controls under double-blind, placebo-controlled conditions. Following m-CPP, but not fenfluramine or placebo, 55% (11/20) of the patients with obsessive-compulsive disorder experienced a transient exacerbation of obsessive-compulsive disorder. Prolactin response was blunted in patients following m-CPP but not following fenfluramine. Patients with greater behavioral response to m-CPP had smaller prolactin responses. Cortisol response to m-CPP and fenfluramine did not significantly differ between the groups. Behavioral and neuroendocrine responses appeared divergent. This does not suggest simply upregulation or downregulation of 5-hydroxytryptamine receptors, but rather complex mechanisms involving multiple neurotransmitter and neuromodulator systems.

Administration, Oral↗
PubMed1992

Effects of fenfluramine on plasma homovanillic acid in healthy subjects.

The specificity of fenfluramine as a pharmacological probe of the serotonin system has been questioned, since animal studies with high dose l-fenfluramine show increases in striatal levels of the dopamine metabolite homovanillic acid. To test the specificity of fenfluramine in humans with clinical doses, we compared plasma homovanillic acid (pHVA) concentration in healthy volunteers after administration of fenfluramine (60 mg) and placebo. There were no significant effects on pHVA, which supports previous findings that at doses used in pharmacological challenge paradigms, the effect of fenfluramine on the dopamine system is insufficient to alter measures of its change.

Dopamine↗
PubMed1992

Neuroendocrine responses to challenge with dl-fenfluramine and aggression in disruptive behavior disorders of children and adolescents.

Prolactin (PRL) and cortisol (CORT) responses to a single oral administration (1.0 mg/kg) of the indirect serotonin agonist dl-fenfluramine were assessed in unmedicated prepubertal and adolescent males with disruptive behavior disorders (DBD). Neuroendocrine responses were correlated with scores on aggression rating scales in prepubertal and adolescent DBD patients and compared with those of matched adolescent normal control subjects. Net dl-fenfluramine-induced PRL and CORT release was not correlated with aggression rating scores in prepubertal and adolescent DBD patients and did not differ significantly between adolescent DBD patients and normal control subjects. Although the present study does not demonstrate a serotonergic abnormality in aggression or DBD, this may be more a reflection of limitations of the neuroendocrine challenge test procedures or the methods used than evidence that serotonergic function in the central nervous system is normal in aggression.

Adolescent↗
PubMed1992

Hormone responses to fenfluramine and placebo challenge in endogenous depression.

Plasma prolactin and cortisol levels after oral administration of d-l fenfluramine hydrochloride (60 mg) and placebo were examined in 24 endogenously depressed patients and 21 age- and sex-matched normal control subjects in a randomized, double-blind study. Prolactin levels were significantly increased by fenfluramine in both groups, but the response was significantly blunted in the depressed patients compared with the controls. This effect was partially dependent upon elevated baseline cortisol levels in the depressed group and was also influenced by a history of weight loss. Plasma cortisol levels were not increased by fenfluramine in either group. These findings confirm previous reports and suggest that patients with endogenous major depression are characterized by central serotonergic hyporesponsivity. The need to account for baseline effects on hormonal responses to putative serotonergic agents is supported by the findings; however, these effects appear to be less striking when endogenicity is a prominent clinical feature of the depressive syndrome. The apparently complex influence of weight loss on prolactin response to serotonergic challenge remains to be clarified as well as the role played by the bioavailability of the challenge drug and its metabolite.

Adult↗
PubMed1992

Early findings from a pharmacokinetically designed double-blind and placebo-controlled study of lithium for adolescents comorbid with bipolar and substance dependency disorders.

1. This manuscript reports the early findings from a National Institute on Drug Abuse funded study of lithium for adolescents dually diagnosed with bipolar and substance dependency disorders. The authors elected to publish early findings in the hope that it would accomplish a twofold mission. 2. The first part would be to encourage other investigators to participate in research in this area and the second would be to heighten the awareness of clinicians that adolescents presenting with either one of these disorders might also have the other. 3. The early findings demonstrated the feasibility of recruiting, retaining and monitoring this complex population on an outpatient basis. 4. Steady-state serum lithium levels were pharmacokinetically placed in the study range, 0.9-1.3 mEq/L. Preliminary results are encouraging in finding lithium more effective than placebo for alleviating both the substance dependency and the mood disordered symptomatology. 5. The characteristics of the study population to date have been chronicity of both disorders, impairment in the severe range in multiple areas of functioning, and strong family histories for both affective and substance use disorders. The substance dependency was to both alcohol and marijuana; but all subjects also had marked polydrug abuse. 6. In order to best monitor lithium compliance and drug/alcohol use during protocol, randomly timed weekly serum and urine assays were obtained. 7. The implications of these early findings for the outcome of this acute phase study and for the development of longitudinal treatment strategies are discussed.

Adolescent↗
PubMed1992

Vitamin E attenuates the toxic effects of 6-hydroxydopamine on free radical scavenging systems in rat brain.

Rats were divided into the following four groups namely (a) sham-operated control, (b) 6-OHDA-treated, (c) sham-operated vitamin E-fed and (d) Vitamin E-fed treated with 6-OHDA. Total glutathione (GSH) and superoxide dismutase (SOD) were measured in brainstem (BS), striatum (ST), hippocampus, frontal cortex, and nucleus accumbens (N. Acc.). GSH and SOD levels were significantly decreased in all regions of 6-OHDA-treated rats compared to controls. Feeding of vitamin E resulted in a significant reduction of GSH in ST and N. Acc. but caused increases in SOD in BS, ST, and N. Acc. Pretreatment of rats with vitamin E caused significant attenuation of the effects of 6-OHDA on GSH and SOD in most of the brain regions. These results show that vitamin E can spare the scavenging systems from the injurious effects of 6-OHDA.

Animals↗
PubMed1992

Pharmacokinetically designed double-blind placebo-controlled study of nortriptyline in 6- to 12-year-olds with major depressive disorder.

A random assignment, double-blind, placebo-controlled study of nortriptyline in 50 prepubertal 6- to 12-year-olds with Research Diagnostic Criteria and DSM-III major depressive disorder was performed. The protocol included a 2-week placebo wash-out phase and an 8-week double-blind, placebo-controlled phase with weekly plasma level monitoring. Active subjects had their plasma level pharmacokinetically placed at 80 +/- 20 ng/ml by using previously developed tables to determine the starting dose from a plasma level 24 hours after a single dose administered at baseline. The mean plasma level was 89.9 ng/ml. The study population was severely depressed, had a chronic, unremitting course of long duration before the study, had a high percentage of family histories with affective disorder, alcoholism and suicidality, and had a high rate of comorbidity. None of the subjects had ever received tricyclic antidepressants before this study. There was a poor rate of response in both treatment groups (30.8% active, 16.7% placebo). Active subjects did not evidence the anticholinergic side effects reported in adult samples. The implications of these findings for future pharmacotherapy studies of depressed children are discussed.

Child↗
PubMed1992

Baseline and 2- to 3-year follow-up characteristics of placebo-washout responders from the nortriptyline study of depressed 6- to 12-year-olds.

Data are presented on the baseline characteristics and 2- to 3-year follow-up assessments of placebo-washout responders (PWRs) from a previously reported pharmacokinetically designed double-blind placebo-controlled trial of nortriptyline for major depressive disorder in 6- to 12-year-olds. Eleven of the 12 PWRs consented to participate in the follow-up study. At baseline, the only significant difference between the PWRs and the non-PWR subjects was that more females were PWRs. Notably, there were no significant differences with respect to severity, chronicity, age of onset, or comorbid psychopathology. The follow-up assessments showed that the rate of relapse to major depressive disorder and the rate of development of bipolarity were not significantly different for PWRs compared with non-PWRs. The authors discuss these findings vis-à-vis the adult literature and provide recommendations for the use of placebo-washout phases in future double-blind, placebo-controlled psychopharmacology trials in children.

Bipolar Disorder↗
PubMed1992

Pregnancy alters the hemodynamic responses to cocaine in the rat.

To test our hypotheses that the hemodynamic response to cocaine may be altered during pregnancy, cocaine (0.33 mg/kg/min) was infused intravenously to chronically catheterized pregnant and nonpregnant female rats. Cardiac output and regional blood flow were measured, and cocaine concentrations in plasma and tissues, as well as plasma cholinesterase activity were determined. Results were compared between pregnant and nonpregnant groups. Cocaine produced a significant decrease in heart rate, accompanied by a fall in cardiac output, and decreased cerebral, myocardial, and placental blood flow in pregnant rats. The plasma cocaine concentration in pregnant animals was lower than that of nonpregnant ones, but tissue concentrations were similar in both groups. These results indicate that pregnancy enhances cardiovascular responses to subtoxic doses of cocaine. There was little placental transfer of cocaine with a fetal to maternal plasma concentration ratio of 0.28.

Animals↗
PubMed1992

Serum prolactin levels in homosexual and bisexual men with HIV infection.

OBJECTIVE: Prolactin is a neurohormone that may be secreted in response to stress and also has regulatory effects on the immune system. Some, but not all, studies suggest that prolactin levels are higher than normal in persons with HIV infection. The authors measured prolactin levels in HIV-positive and HIV-negative homosexual and bisexual men to assess possible differences in levels and then examined relationships between prolactin level and measures of medical status, anxiety, depression, stress, and neuropsychological test performance. METHOD: Blood for prolactin level determination was obtained from 121 HIV-seropositive and 79 HIV-seronegative homosexual and bisexual men enrolled in a longitudinal study. The men also underwent a daylong assessment that included medical, immunological, psychiatric, psychosocial, psychosexual, and neuropsychological evaluations. RESULTS: There was no statistically significant difference in serum prolactin level among the seronegative men, the seropositive men with no or minimal physical symptoms, and the seropositive men with significant physical symptoms of HIV infection. Furthermore, within the HIV-seropositive group, the correlations between serum prolactin level and measures of depression, anxiety, stress, and neuropsychological test performance were all nonsignificant. CONCLUSIONS: Serum prolactin level does not seem to respond to HIV infection or to be related to stress or psychiatric symptoms in HIV-infected men. As none of the subjects had AIDS, the possibility cannot be ruled out that prolactin level increases in very late stages of HIV infection.

Adult↗
PubMed1992

Sensitive and selective liquid-chromatographic assay of fluoxetine and norfluoxetine in plasma with fluorescence detection after precolumn derivatization.

We determined fluoxetine (Prozac) and its major metabolite norfluoxetine in plasma by liquid chromatography with fluorescence detection. After liquid-liquid extraction from 1 mL of plasma, the extract was derivatized at room temperature with dansyl chloride, and the highly fluorescent derivatives were chromatographed with a reversed-phase C18 column and a mobile phase of phosphate buffer and acetonitrile. Dansylated fluoxetine, norfluoxetine, and the internal standard were eluted in less than 14 min with no interference from endogenous material. The calibration curve was linear over the concentration range 25-800 micrograms/L with inter- and intra-assay imprecision (CV) of less than 10%. Validity of the assay was checked by comparing results for 110 patients' samples with those by a liquid-chromatographic method with ultraviolet detection (r = 0.993 for fluoxetine, 0.957 for norfluoxetine). The identity of the dansylated derivatives was verified by positive chemical ionization mass spectroscopy. The lower limit of detection was approximately 3 micrograms/L. Because no major antidepressant, neuroleptic, or respective drug metabolites interfere with the quantification of fluoxetine and norfluoxetine, this is a useful procedure for pharmacokinetic studies and in clinical settings.

Chromatography, Liquid↗
PubMed1991

Effect of extended depot fluphenazine treatment and withdrawal on social and other behaviors of Cebus apella monkeys.

To examine whether or not prolonged exposure to a depot neuroleptic has either residual or "tardive pathological" effects on normal behavior, 38 Cebus apella monkeys were observed daily for 108 weeks. The issue of stress influencing such effects was also addressed. During weeks 25-48 half of the monkeys received 0.22 mg/kg fluphenazine decanoate, IM, every 3 weeks, with the dose increased to 0.33 mg/kg during weeks 49-72. Behavioral measures were combined to form composite behavioral variables which quantify four major aspects of behavior: self- and environment-directed behavior, affiliation, aggression, and normal locomotor activity. Mean plasma fluphenazine levels at 48 h post-injection were 0.13 (+/- 0.03) ng/ml for injections 3-8 and 0.24 (+/- 0.07) ng/ml for injections 11-16. The pre-study null hypothesis that the four major aspects of behavior would not be adversely affected by this treatment during the drug-discontinuation phase of the study (weeks 73-108) was not statistically negated. There were highly significant decreases in self- and environment-directed behaviors and affiliation during the treatment periods, implying that treatment may contribute to the negative symptoms of treated schizophrenics. Stress reduced the above effects. Aggression showed some increase during early drug discontinuation, accentuated by stress. Recovery of normal (baseline) behavioral scores began by week 7 after the last treatment. Mild (bucco-lingual) tardive dyskinesias persisted in 30% of the animals for a prolonged time.

Animals↗
PubMed1991

Disappearance of memory deficits in outpatient depressives responding to imipramine.

We evaluated learning and memory in 50 depressed patients prior to and following 4 week treatment with imipramine compared to 21 normal controls tested at corresponding times. At baseline, the depressives did worse than normals on most memory tasks with the difficult memory tasks, regardless of store, modality or type of task best distinguishing between depressive and normal memory. Following imipramine treatment, responders performed better than nonresponders on the difficult memory tasks, and not significantly differently from controls on most tasks. This, as well as the fact that the responders improved to a greater degree than controls on most measures (in a few cases the difference was statistically significant) and the fact that at 4 weeks complete responders to imipramine did significantly better than partial responders to imipramine, indicates that relief from depression is highly related to improved memory functioning. The finding that complete responders to imipramine were not significantly worse than normal controls suggests that imipramine did not have significant adverse effects on memory.

Adult↗